Flashcards in Myelodysplastic Syndrome &Myeloproliferative Neoplasms Deck (50):
Define myelodysplastic syndrome.
A group of clonal hematopoietic stem cell disorders characterized by
-Increased risk of transformation to acute myeloid leukemia
What are the two types of clinical scenarios of MDS?
1. Primary/ Idiopathic: Patients usually over 50yrs
2. Increased risk of transformation to acute myeloid leukemia
Persistent cytopenias of two or more lineages in an elderly patient would suggest what syndrome?
Myelodysplastic syndrome. The clones replace the marrow to a varying extent thus decreasing physical space in which other lineages can replicate
What should you see on evaluation of bone marrow of a patient with MDS?
What is dyserythropoiesis?
RBC precursors with nuclear budding, irregularly-shaped nuclei, lack of coordination between nuclear and cytoplasmic maturation, increased ring sideroblasts.
What is dysgranulopoiesis?
Nuclear hypolobation of mature neutrophils, including neutrophils with bilobed nuclei called pseudo-Pelger-Huet cells, also cytoplasmic hypogranularity of neutrophils
What is dysmegakaryopoiesis?
Megakaryocytes with hypolobated or non-lobated nuclei, often hyperchromatic nuclei, megakaryocytes often of small size.
What would the karyotypes of a person with MDS look like?
What are some secondary causes of MDS?
-Deficiencies of Vitamin B12, folic acid, or certain essential elements
-Toxin exposure, especially heavy metals
What is low grade MDS?
Myeloblasts account for less than 5% of marrow cells, and less than 2% of peripheral blood cells
What is high grade MDS?
Myeloblasts account for 5% or more of marrow cells, and/or 2% of peripheral blood cells
What are the three types of low grade MDS?
1. Refractory cytopenias with unilineage dysplasia
2. Refractory cytopenias with multilineage dysplasia
3. MDS with Isolated deletion 5q
What is the prognosis of a patient with RC-UD?
Good. Only 2% of cases transform to AML
What is the prognosis of RC-MD?
Median survival of 2.5 years
Rate of transformation 10% at 2 years
Which type of low grade MDS is associated with anemia, increased platelets, and marrow showing distinctive megakaryocytes with small, round, non-lobated nuclei?
MDS with isolated deletion 5q
What are the two types of high grade MDS?
1. Refractory anemia with excess blasts-1 (RAEB-1): marrow blasts= 2-9% and peripheral blood 2-4%
2. Refractory anemia with excess blasts-II (RAEB-II): marrow blasts = 10-19% and peripheral blood= 5-19%
What is the prognosis of high grade MDS?
Poor diagnosis most patients die from bone marrow failure before transformation to AML
What is the treatment of patients with MDS?
Allogeneic stem cell transplant
Supportive care- including transfusions
Describe the characteristics of myeloproliferate neoplasms (MPNs).
Proliferation of one or more myeloid lineages usually seen in adults in their 50s-70s
Name the phenotypic presentation of MPNs.
1. Hypercellular marrow
2. Splenomegaly and/or hepatomegaly
What causes splenomegaly and/or hepatomegaly in patients with MPNs?
1. Sequestration of excess blood cells
2. Extramedullary hematopoiesis
What are three outcomes of untreated MPNs?
1. Transformation to acute leukemia
2. Development of Myelodysplasia with ineffective hematopoiesis
3. Excessive marrow fibrosis with resultant bone marrow failure
What genes are commonly mutated in MPNs?
Genes that encode for cytoplasmic or receptor protein tyrosine kinases (PTKs)
What are the four classifications of myeloproliferative neoplasms?
1. Chronic myelogenous leukemia (CML)
2. Polycythemia vera (PV)
3. Primary myelofibrosis (PMF)
4. Essential thrombocythemia (ET)
What is the definition of CML?
CML is a clonal hematopoietic stem cell disorder, associated with the presence of the BCR-ABL1 gene fusion, and most prominently manifesting as a prominent neutrophilic leukocytosis
What are the clinical findings of a patient with CML?
Initial symptoms- Fatigue, weight loss, night sweats, splenomegaly, and anemia.
What is the typical age at diagnosis for CML?
40s and 50s
What is the chronic phase of CML?
It is the initial phase in which blasts are not significantly increased in the marrow or blood
-Thrombocytopenia (although can be within normal range)q
How does the bone marrow appear in a patient with chronic myelogenous leukemia?
Hypercellular marrow due to granulocytic hyperplasia.
Small megakaryocytes with round, non-lobulated nuclei
What would happen if CML was left untreated?
It would rapidly progress to acute leukemia with 20% or more blasts in the marrow or blood
What would be the course of CML to Acute leukemia?
Chronic Myelogenous Leukemia>>>>Accelerated phase>>>Blast phase
What genetic perturbation partially defines CML?
BCR-ABL1 gene fusion resulting from a translocation (9;22)(q34;q11.2)
Derivative chromosome 22, which is referred to as the Philadelphia Chromosome
Two proteins could be produced:
How can you diagnose BCR-ABL fusion?
3. RT-PCR of BCR-ABL mRNA transcripts
What is the treatment of someone with CML?
-Gleevac protein tyrosin kinase inhibitor (first gen)
-Dasatinib protein tyrosin kinase inhibitor (second gen)
What is polycythemia vera (PV)?
Myeloproliferative neoplasm characterized primarily by an increase in RBC mass (erythrocytosis) accompanied by an increase in neutrophils and platelets.
What gene is mutated in PV?
Nearly all cases of PV contain a mutation of the JAK2 gene encoding the JAK2 cell signaling protein
Most contain the V617F point mutation
What if a patient has erythrocytosis and doesn't have JAK2 gene mutation?
Could be secondary erythrocytosis due to smoking or chronic hypoxia
What are the two stages of polycythemia vera?
1. Polycythemic Stage- increased peripheral blood cell counts
2. Spent Phase-Marrow shows prominent fibrosis and peripheral blood cell counts fall
What is the most common complication of PV?
Venous or arterial thrombosis that can present as:
True or False:
-The possibility of PV should always be considered in a patient with thrombosis of the mesenteric vein, portal vein, or splenic vein.
What is the genetic mutation found in 50% of primary myelofibrosis?
Mutations of JAK2
Describe the prefibrotic stage.
Marrow is hypercellular- granulocytic and megakaryocytic proliferation
Megakaryocytes are large, bizarre and are found in others
During the fibrotic stage there is significant reticulin fibrosis with loss of marrow space. Hematopoiesis then occurs in the marrow sinusoids. What is this called?
Intramedullary extramedullary hematopoiesis
What is seen in the peripheral blood of patients with primary myelofibrosis in the fibrotic stage?
Leukoerythroblastosis- Increased immature granulocytes and increased immature nucleated red blood cells (tear drop shape)
Extramedullary hematopoiesis also occurs in primary myelofibrosis. Where may this occur?
Spleen, liver, lymph nodes, and other organs
When is primary myelofibrosis diagnosed?
Not diagnosed until the fibrotic stage
Median survival around 5 years
How does essential thrombocythemia different from primary myelofibrosis?
ET only has marked thrombocytosis, but no granulocytic hyperplasia in the the marrow (this is PMF)
What genetic mutation is found in 50% of all essential thrombocythemia (ET) ?
What are four signs and symptoms of ET?
-Transient ischemic attacks
-digital ischemia with paresthesias
-thrombosis of major arteries or veins
-Splenomegaly is NOT COMMON